目的近几年来发表的数据显示成纤维细胞生长因子(FGFs),包括FGF1,FGF19和FGF21,具有类似于胰岛素的代谢调节功能。例如,在饮食诱导的糖尿病小鼠中,FGF1的单次注射足以使血糖水平恢复到正常范围;同时FGF19或FGF21过表达可以校正糖耐量受损的小鼠。在细胞表面,FGFs通过FGF受体(FGFR)和糖胺聚糖进行信号传导。FGF1与属于糖胺聚糖的肝素具有高亲和力,而FGF19和FGF21与肝素无亲和力。糖胺聚糖结构多样,是信息含量最高的生物大分子。作者认为如果非肝素类多糖可以刺激FGF19/FGFR和FGF21/FGFR的信号传导,这类化合物有可能成为调节代谢疾病的新型药物。方法采用表达FGFR1c的BaF3细胞作为筛选具有活性多糖与寡糖的模型。结果发现聚甘露糖醛酸硫酸酯(PMS)及寡糖(PMS12及PMS25)可以增强FGF19和FGF21介导下的BaF3细胞中3 H-胸苷嘧啶标记的DNA合成,而聚甘露糖醛酸(PM)无此作用。此外,PMS,PMS寡糖包括其二糖与肝素类似具有增强FGF1/FGFR1c信号通路介导的BaF3的细胞增殖作用。结论由于PMS及其寡糖可通过口服途径被吸收,因此这些廉价的海藻酸衍生物有可能通过增强FGF1/FGFR1c,FGF19/FGFR1c和FGF21/FGFR1c的信号传导而被开发成为治疗2型糖尿病的新型口服药物。 Objectives Published data in recent years show that fibroblast growth factors (FGFs), including FGF1, FGF19 and FGF21, have insulin-like metabolic regulatory functions. For example, in a diet-induced diabetic mouse, a single injection of FGFl is sufficient to restore blood glucose levels to the normal range; while FGF19 or FGF21 overexpression corrects impaired glucose tolerance in mice. On the cell surface, FGFs signal through the FGF receptor (FGFR) and glycosaminoglycans. FGF1 has a high affinity for heparin belonging to glycosaminoglycans whereas FGF19 and FGF21 have no affinity for heparin. Glycosaminoglycans are diverse in structure and are the most informative biological macromolecules. The authors conclude that if non-heparin polysaccharides stimulate the signaling of FGF19 / FGFR and FGF21 / FGFR, these compounds are likely to become new drugs for the regulation of metabolic diseases. Methods BaF3 cells expressing FGFR1c were used as a model for screening active polysaccharides and oligosaccharides. As a result, polymannuronic acid sulfate (PMS) and oligosaccharides (PMS12 and PMS25) were found to enhance 3 H-thymidine-labeled DNA synthesis in BaF3 cells mediated by FGF19 and FGF21, whereas polymannuronic acid PM) no such effect. In addition, PMS, PMS oligosaccharides, including their disaccharides, like heparin, have the effect of enhancing the cell proliferation of the FGF1 / FGFR1c signaling pathway mediated by BaF3. Conclusions Since PMS and its oligosaccharides can be absorbed orally, it is possible that these inexpensive derivatives of alginic acid have been developed as new types of treatment for type 2 diabetes by enhancing the signaling of FGF1 / FGFR1c, FGF19 / FGFR1c and FGF21 / FGFR1c Oral drugs.